Type 2 Diabetes Mellitus Who Have Been Examined at a Medical Institution
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to determine the safety and efficacy of long-term treatment with alogliptin (Nesina) in patients with type 2 diabetes mellitus who responded inadequately to diet therapy and exercise therapy alone, or a combination of diet therapy, exercise therapy, and α-glucosidase inhibitor. In addition, examining the safety and efficacy of alogliptin in patients with renal impairment, information on the appropriate dosage of alogliptin according to the severity of impaired renal function should be collected.
Detailed description
A special drug use surveillance is planned to examine the safety and efficacy of long-term use of alogliptin in patients with type 2 diabetes mellitus under the daily clinical use conditions. Participants of this surveillance will be patients with type 2 diabetes mellitus who failed to respond adequately to diet therapy and exercise therapy alone or to a combination of diet therapy, exercise therapy, and α-glucosidase inhibitor. The planned sample size is 3,000 subjects. The usual adult dosage for oral use is 1 alogliptin tablet (25 mg) once daily. Participants will receive the drug as part of routine medical care.
Interventions
DRUGAlogliptin
Alogliptin tablets
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with type 2 diabetes mellitus who have not adequately responded to any one of the following therapies: 1. Diet therapy and exercise therapy alone 2. In addition to diet therapy and exercise therapy, use of α-glucosidase inhibitor
Exclusion criteria
* Patients contraindicated for Nesina 1. Patients with severe ketosis, diabetic coma or precoma, or type 1 diabetes mellitus (these patients require prompt adjustment of hyperglycemia by fluid infusion and insulin, and hence use of Nesina is not appropriate.) 2. Patients with severe infection, pre- or post-operative patients, or patients with serious traumatic injury (blood glucose control by insulin injection is desirable for these patients, and hence use of Nesina is not appropriate.) 3. Patients with a history of hypersensitivity to any ingredient of Nesina
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience at Least One Adverse Events | Up to Month 36 | — |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline, Months 1, 3, 6, 12, 18, 24, 30, 36 and final assessment (up to Month 36) | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at month 36 relative to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Blood Glucose | Baseline, Months 1, 3, 6, 12, 18, 24, 30, 36 and final assessment (up to Month 36) | The change in the value of fasting blood glucose collected at month 36 relative to baseline. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 608 investigative sites in Japan, from 8-July-2010 to 31-October-2015. Data reports overall population, since data not collected separately per arm as specified in protocol.
Pre-assignment details
Participants with type 2 diabetes mellitus who failed to respond adequately to diet and/or exercise therapy and α-glucosidase inhibitor were enrolled to receive Alogliptin as routine medical care. Treatments were not allocated at the start of the study. Thus, the Participant Flow cannot be presented per Arm.
Participants by arm
| Arm | Count |
|---|---|
| Alogliptin Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received no diabetic drugs within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin. | 1,560 |
| Alogliptin + αGI Alogliptin 25 mg, tablets, orally, once daily for up to 36 months in routine medical care. Participants in this group received an α-GI within 3 months from the start of administration of alogliptin and during the treatment period of alogliptin. | 669 |
| Alogliptin + Other Alogliptin 25 mg, tablets, orally, once daily for up to 12 months in routine medical care. Participants in this group did not receive an α-GI within 3 months from the start of administration of alogliptin or during the treatment period of alogliptin. | 989 |
| Total | 3,218 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Case report forms (CRF) uncollected | 52 |
| Overall Study | CRF not assured by investigators | 5 |
| Overall Study | Protocol Violation | 42 |
Baseline characteristics
| Characteristic | Alogliptin | Alogliptin + αGI | Alogliptin + Other | Total |
|---|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 12.28 | 67.1 years STANDARD_DEVIATION 12.13 | 64.0 years STANDARD_DEVIATION 12.57 | 65.1 years STANDARD_DEVIATION 12.39 |
| Alcohol Consumption Classification Drinking Almost Everyday | 412 Participants | 158 Participants | 276 Participants | 846 Participants |
| Alcohol Consumption Classification Not Drinking Almost Everyday | 891 Participants | 383 Participants | 526 Participants | 1800 Participants |
| Alcohol Consumption Classification Unknown | 257 Participants | 128 Participants | 187 Participants | 572 Participants |
| Allergic Disease Complications Had Allergic Disease Complications | 94 Participants | 42 Participants | 75 Participants | 211 Participants |
| Allergic Disease Complications Had No Allergic Disease Complications | 1466 Participants | 627 Participants | 914 Participants | 3007 Participants |
| BMI | 25.00 kg/m^2 STANDARD_DEVIATION 4.225 | 24.52 kg/m^2 STANDARD_DEVIATION 4.277 | 25.04 kg/m^2 STANDARD_DEVIATION 4.19 | 24.91 kg/m^2 STANDARD_DEVIATION 4.229 |
| Body Weight | 64.49 kg STANDARD_DEVIATION 13.699 | 62.68 kg STANDARD_DEVIATION 13.005 | 64.51 kg STANDARD_DEVIATION 14.046 | 64.12 kg STANDARD_DEVIATION 13.681 |
| Cardiac Disease Complications Had Cardiac Disease Complications | 143 Participants | 91 Participants | 119 Participants | 353 Participants |
| Cardiac Disease Complications Had No Cardiac Disease Complications | 1417 Participants | 578 Participants | 870 Participants | 2865 Participants |
| Complications Had Complications | 1246 Participants | 608 Participants | 886 Participants | 2740 Participants |
| Complications Had No Complications | 314 Participants | 61 Participants | 103 Participants | 478 Participants |
| Degree of Hepatic Dysfunction Grade 1 | 122 Participants | 36 Participants | 87 Participants | 245 Participants |
| Degree of Hepatic Dysfunction Grade 2 | 22 Participants | 10 Participants | 19 Participants | 51 Participants |
| Degree of Hepatic Dysfunction Grade 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Degree of Hepatic Dysfunction Normal | 986 Participants | 443 Participants | 596 Participants | 2025 Participants |
| Degree of Hepatic Dysfunction Unknown | 430 Participants | 180 Participants | 287 Participants | 897 Participants |
| Degree of Renal Dysfunction (Cr) Moderate | 24 Participants | 7 Participants | 17 Participants | 48 Participants |
| Degree of Renal Dysfunction (Cr) Normal or Mild | 1089 Participants | 466 Participants | 664 Participants | 2219 Participants |
| Degree of Renal Dysfunction (Cr) Severe | 21 Participants | 19 Participants | 15 Participants | 55 Participants |
| Degree of Renal Dysfunction (Cr) Unknown | 426 Participants | 177 Participants | 293 Participants | 896 Participants |
| Degree of Renal Dysfunction (eGFR) Mild | 667 Participants | 254 Participants | 361 Participants | 1282 Participants |
| Degree of Renal Dysfunction (eGFR) Moderate | 190 Participants | 108 Participants | 121 Participants | 419 Participants |
| Degree of Renal Dysfunction (eGFR) Normal | 249 Participants | 108 Participants | 189 Participants | 546 Participants |
| Degree of Renal Dysfunction (eGFR) Severe | 28 Participants | 22 Participants | 25 Participants | 75 Participants |
| Degree of Renal Dysfunction (eGFR) Unknown | 426 Participants | 177 Participants | 293 Participants | 896 Participants |
| Diabetic Complications Had Diabetic Complications | 158 Participants | 163 Participants | 158 Participants | 479 Participants |
| Diabetic Complications Had No Diabetic Complications | 1402 Participants | 506 Participants | 831 Participants | 2739 Participants |
| Glycosylated Hemoglobin A1c (HbA1c) HbA1c <6.0 percent | 28 Participants | 24 Participants | 33 Participants | 85 Participants |
| Glycosylated Hemoglobin A1c (HbA1c) HbA1c >=6.0 to <7.0 percent | 475 Participants | 134 Participants | 195 Participants | 804 Participants |
| Glycosylated Hemoglobin A1c (HbA1c) HbA1c >=7.0 to <8.0 percent | 576 Participants | 270 Participants | 320 Participants | 1166 Participants |
| Glycosylated Hemoglobin A1c (HbA1c) HbA1c >=8.0 percent | 351 Participants | 195 Participants | 345 Participants | 891 Participants |
| Glycosylated Hemoglobin A1c (HbA1c) Unknown | 130 Participants | 46 Participants | 96 Participants | 272 Participants |
| Healthcare category In-patient | 3 Participants | 8 Participants | 11 Participants | 22 Participants |
| Healthcare category In- to/from out-patient | 33 Participants | 21 Participants | 36 Participants | 90 Participants |
| Healthcare category Out-patient | 1524 Participants | 640 Participants | 942 Participants | 3106 Participants |
| Heart Failure Complications Had Heart Failure Complications | 43 Participants | 20 Participants | 19 Participants | 82 Participants |
| Heart Failure Complications Had No Heart Failure Complications | 1517 Participants | 649 Participants | 970 Participants | 3136 Participants |
| Height | 160.22 cm STANDARD_DEVIATION 9.686 | 159.33 cm STANDARD_DEVIATION 9.535 | 160.18 cm STANDARD_DEVIATION 9.738 | 160.02 cm STANDARD_DEVIATION 9.674 |
| Hepatic Dysfunction Complications Had Hepatic Dysfunction Complications | 238 Participants | 116 Participants | 190 Participants | 544 Participants |
| Hepatic Dysfunction Complications Had No Hepatic Dysfunction Complications | 1322 Participants | 553 Participants | 799 Participants | 2674 Participants |
| History of Allergy Had history of Allergy | 127 Participants | 57 Participants | 104 Participants | 288 Participants |
| History of Allergy Had no history of Allergy | 1377 Participants | 583 Participants | 856 Participants | 2816 Participants |
| History of Allergy Unknown | 56 Participants | 29 Participants | 29 Participants | 114 Participants |
| Hyperlipidemia Complications Had Hyperlipidemia Complications | 845 Participants | 423 Participants | 614 Participants | 1882 Participants |
| Hyperlipidemia Complications Had No Hyperlipidemia Complications | 715 Participants | 246 Participants | 375 Participants | 1336 Participants |
| Hypertension Complications Had Hypertension Complications | 884 Participants | 420 Participants | 606 Participants | 1910 Participants |
| Hypertension Complications Had No Hypertension Complications | 676 Participants | 249 Participants | 383 Participants | 1308 Participants |
| Hyperuricemia Complications Had Hyperuricemia Complications | 149 Participants | 58 Participants | 98 Participants | 305 Participants |
| Hyperuricemia Complications Had No Hyperuricemia Complications | 1411 Participants | 611 Participants | 891 Participants | 2913 Participants |
| Malignancy Complications Had Malignancy Complications | 17 Participants | 8 Participants | 29 Participants | 54 Participants |
| Malignancy Complications Had No Malignancy Complications | 1543 Participants | 661 Participants | 960 Participants | 3164 Participants |
| Medical history Had Medical History | 225 Participants | 126 Participants | 166 Participants | 517 Participants |
| Medical history Had No Medical History | 1255 Participants | 501 Participants | 768 Participants | 2524 Participants |
| Medical history Unknown | 80 Participants | 42 Participants | 55 Participants | 177 Participants |
| New York Heart Association (NYHA) Heart Failure Classification NYHA Class I | 26 Participants | 13 Participants | 11 Participants | 50 Participants |
| New York Heart Association (NYHA) Heart Failure Classification NYHA Class II | 16 Participants | 5 Participants | 5 Participants | 26 Participants |
| New York Heart Association (NYHA) Heart Failure Classification NYHA Class III | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| New York Heart Association (NYHA) Heart Failure Classification NYHA Class IV | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| New York Heart Association (NYHA) Heart Failure Classification Unknown | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Pregnancy Status Not pregnant | 640 Participants | 286 Participants | 438 Participants | 1364 Participants |
| Pregnancy Status Pregnant | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment Japan | 1560 Participants | 669 Participants | 989 Participants | 3218 Participants |
| Renal Dysfunction Complications Had No Renal Dysfunction Complications | 1427 Participants | 563 Participants | 861 Participants | 2851 Participants |
| Renal Dysfunction Complications Had Renal Dysfunction Complications | 133 Participants | 106 Participants | 128 Participants | 367 Participants |
| Sex: Female, Male Female | 640 Participants | 286 Participants | 438 Participants | 1364 Participants |
| Sex: Female, Male Male | 920 Participants | 383 Participants | 551 Participants | 1854 Participants |
| Smoking Classification Current Smoker | 227 Participants | 77 Participants | 155 Participants | 459 Participants |
| Smoking Classification Ex-Smoker | 249 Participants | 153 Participants | 160 Participants | 562 Participants |
| Smoking Classification Never Smoked | 737 Participants | 292 Participants | 414 Participants | 1443 Participants |
| Smoking Classification Unknown | 347 Participants | 147 Participants | 260 Participants | 754 Participants |
| Stroke-Related Disorder Complications Had No Stroke-Related Disorder Complications | 1505 Participants | 613 Participants | 922 Participants | 3040 Participants |
| Stroke-Related Disorder Complications Had Stroke-Related Disorder Complications | 55 Participants | 56 Participants | 67 Participants | 178 Participants |
| Time From Diagnosis of Type 2 Diabetes | 3.45 years STANDARD_DEVIATION 4.923 | 8.10 years STANDARD_DEVIATION 7.018 | 5.03 years STANDARD_DEVIATION 5.732 | 4.91 years STANDARD_DEVIATION 5.937 |
| Waist Circumference (Female) < 90cm | 152 Participants | 65 Participants | 85 Participants | 302 Participants |
| Waist Circumference (Female) ≥ 90cm | 70 Participants | 37 Participants | 52 Participants | 159 Participants |
| Waist Circumference (Female) Unknown | 418 Participants | 184 Participants | 301 Participants | 903 Participants |
| Waist Circumference (Male) < 85cm | 96 Participants | 55 Participants | 61 Participants | 212 Participants |
| Waist Circumference (Male) ≥ 85cm | 211 Participants | 80 Participants | 120 Participants | 411 Participants |
| Waist Circumference (Male) Unknown | 613 Participants | 248 Participants | 370 Participants | 1231 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1,560 | 1 / 669 | 2 / 989 |
| other Total, other adverse events | 26 / 1,560 | 19 / 669 | 23 / 989 |
| serious Total, serious adverse events | 2 / 1,560 | 2 / 669 | 8 / 989 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at month 36 relative to baseline.
Time frame: Baseline, Months 1, 3, 6, 12, 18, 24, 30, 36 and final assessment (up to Month 36)
Population: The efficacy assessment population was defined as participants who completed the study and had available efficacy data at baseline and post baseline. Reported group were Alogliptin and Alogliptin + α-GI and data for Alogliptin + Other were not collected as specified in protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 1 | -0.45 Percent | Standard Deviation 0.581 |
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 12 | -0.83 Percent | Standard Deviation 1.102 |
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 30 | -0.83 Percent | Standard Deviation 1.114 |
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 18 | -0.81 Percent | Standard Deviation 1.077 |
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 3 | -0.79 Percent | Standard Deviation 1.007 |
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 24 | -0.82 Percent | Standard Deviation 1.095 |
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Final Assessment | -0.81 Percent | Standard Deviation 1.14 |
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 36 | -0.84 Percent | Standard Deviation 1.131 |
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 6 | -0.84 Percent | Standard Deviation 1.045 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Final Assessment | -0.63 Percent | Standard Deviation 1.381 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 36 | -0.72 Percent | Standard Deviation 1.318 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 1 | -0.33 Percent | Standard Deviation 0.708 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 3 | -0.54 Percent | Standard Deviation 1.074 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 6 | -0.70 Percent | Standard Deviation 1.128 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 12 | -0.75 Percent | Standard Deviation 1.054 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 18 | -0.62 Percent | Standard Deviation 1.19 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 30 | -0.73 Percent | Standard Deviation 1.271 |
| Alogliptin + α-GI | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Change at Month 24 | -0.66 Percent | Standard Deviation 1.214 |
Primary
Number of Participants Who Experience at Least One Adverse Events
Time frame: Up to Month 36
Population: Safety Analysis Set was defined as all participants who were enrolled and completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alogliptin | Number of Participants Who Experience at Least One Adverse Events | 151 Participants |
| Alogliptin + α-GI | Number of Participants Who Experience at Least One Adverse Events | 98 Participants |
| Alogliptin + Other | Number of Participants Who Experience at Least One Adverse Events | 139 Participants |
Secondary
Change From Baseline in Fasting Blood Glucose
The change in the value of fasting blood glucose collected at month 36 relative to baseline.
Time frame: Baseline, Months 1, 3, 6, 12, 18, 24, 30, 36 and final assessment (up to Month 36)
Population: The efficacy assessment population was defined as participants who completed the study and had available efficacy data at baseline and post baseline. Reported group were Alogliptin and Alogliptin + α-GI and data for Alogliptin + Other were not collected as specified in protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Month 12 | -23.1 mg/dL | Standard Deviation 43.6 |
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Month 30 | -24.4 mg/dL | Standard Deviation 39.14 |
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Month 1 | -22.9 mg/dL | Standard Deviation 45.05 |
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Month 3 | -21.7 mg/dL | Standard Deviation 39.4 |
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Month 6 | -19.1 mg/dL | Standard Deviation 36.46 |
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Month 18 | -21.1 mg/dL | Standard Deviation 41.54 |
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Month 24 | -19.9 mg/dL | Standard Deviation 42.56 |
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Month 36 | -23.0 mg/dL | Standard Deviation 45.19 |
| Alogliptin | Change From Baseline in Fasting Blood Glucose | Change at Final Assessment | -24.5 mg/dL | Standard Deviation 48.45 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Month 36 | -18.6 mg/dL | Standard Deviation 48.8 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Month 12 | -18.4 mg/dL | Standard Deviation 41.37 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Month 24 | -14.0 mg/dL | Standard Deviation 42.09 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Month 6 | -14.5 mg/dL | Standard Deviation 49.9 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Month 30 | -11.7 mg/dL | Standard Deviation 52.27 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Final Assessment | -12.2 mg/dL | Standard Deviation 51.25 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Month 1 | -4.9 mg/dL | Standard Deviation 41.17 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Month 18 | -16.0 mg/dL | Standard Deviation 46.75 |
| Alogliptin + α-GI | Change From Baseline in Fasting Blood Glucose | Change at Month 3 | -8.3 mg/dL | Standard Deviation 36.58 |